A number of well-designed epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of Alzheimer's disease (AD). Several mechanisms could help to explain this ...proposed link, including insulin and insulin resistance, inflammatory cytokines, and oxidative stress. Obesity or physical inactivity might also influence AD through effects on hypertension, insulin sensitivity or inflammation. Typical AD pathology, such as amyloid-beta deposits, might be exacerbated by insulin dysregulation, T2DM itself, or microvascular disease that is a consequence of T2DM. T2DM patients are not routinely evaluated for cognitive outcomes, and cognitive impairment in T2DM is rarely treated. Similarly, AD patients are not routinely evaluated for T2DM or hyperinsulinemia. Current treatments for AD have only modest benefits, and several drugs that target metabolic and inflammatory pathways are being evaluated, most notably the statins, which reduce LDL and inflammation but might not influence amyloid- deposition, an important precursor for AD. Although some evidence supports a potentially important role for peroxisome proliferative activated receptor agonists such as glitazones, at present there are no published randomized clinical trials in AD patients of any drugs that target insulin or insulin resistance. Clinical implications of the T2DM-AD link include cognitive evaluations of patients with T2DM, and potential benefits for such patients through treatment with statins or diabetes drugs that target insulin.
To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.
Findings were pooled from 5 ...population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.
After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.
Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the ...association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death.
This study included 1,617 participants 60-98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models.
Participants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 95% CI 1.65-2.73 and 2.15 1.58-2.95) and dementia/CIND (2.48 1.75-3.51) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 1.41-2.97 and 1.55 0.93-2.58) compared with those without diabetes.
These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.
This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from ...the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60–101 years) in California followed in 1998–2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.
With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk ...factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.
We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.
These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Detection of “any cognitive impairment” is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives. Methods We ...developed and validated a brief Dementia Screening Indicator using data from four large, ongoing cohort studies (the Cardiovascular Health Study CHS; the Framingham Heart Study FHS; the Health and Retirement Study HRS; the Sacramento Area Latino Study on Aging SALSA) to help clinicians identify a subgroup of high-risk patients to target for cognitive screening. Results The final Dementia Screening Indicator included age (1 point/year; ages, 65–79 years), less than 12 years of education (9 points), stroke (6 points), diabetes mellitus (3 points), body mass index less than 18.5 kg/m2 (8 points), requiring assistance with money or medications (10 points), and depressive symptoms (6 points). Accuracy was good across the cohorts (Harrell's C statistic: CHS, 0.68; FHS, 0.77; HRS, 0.76; SALSA, 0.78). Conclusions The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening.
Abstract
Low- and middle-income countries (LMICs) are experiencing rapid aging, a growing dementia burden, and relatively high rates of out-migration among working-age adults. Family member migration ...status may be a unique societal determinant of cognitive aging in LMIC settings. We aimed to evaluate the association between adult child US migration status and change in cognitive performance scores using data from the Mexican Health and Aging Study, a population-based, national-level cohort study of Mexico adults aged ≥50 years at baseline (2001), with 2-, 12-, and 14-year follow-up waves (2003, 2012, and 2015). Cognitive performance assessments were completed by 5,972 and 4,939 respondents at 11 years and 14 years of follow-up, respectively. For women, having an adult child in the United States was associated with steeper decline in verbal memory scores (e.g., for 9-year change in immediate verbal recall z score, marginal risk difference (RD) = –0.09 (95% confidence interval (CI): −0.16, −0.03); for delayed verbal recall z score, RD = –0.10 (95% CI: −0.17, −0.03)) and overall cognitive performance (for overall cognitive performance z score, RD = –0.04, 95% CI: −0.07, −0.00). There were mostly null associations for men. To our knowledge, this is the first study to have evaluated the association between family member migration status and cognitive decline; future work should be extended to other LMICs facing population aging.
Objectives
To describe the association between restricted life‐space and characteristics of community‐dwelling adults hospitalized for congestive heart failure (CHF) or chronic obstructive pulmonary ...disease (COPD), to estimate the effect of hospitalization on postdischarge mobility, and to determine whether baseline restricted life‐space predicts hospital readmission.
Design
Observational.
Setting
Urban academic hospital that serves as a safety net for urban and rural populations with low resources and serves central and northern Alabama.
Participants
Individuals with CHF or COPD hospitalized from home (N = 478).
Measurements
The Life‐Space Assessment (LSA) measures mobility by asking about movement in situations ranging from within one's dwelling to beyond one's town. LSA scores below 60 correspond to “restricted life‐space.” Baseline LSA scores before admission were measured during an index hospitalization; follow‐up LSA scores were determined over the telephone at 90 days. Participant characteristics were examined according to baseline restricted life‐space using the chi‐square test and Student's t‐test. Each characteristic's association with restricted life‐space was estimated uisng logistic regression.
Results
Of the participants, 372 (77.8%) were classified as having baseline restricted life‐space. Baseline restricted life‐space was associated with older age (odds ratio (OR) = 1.29 per decade, 95% confidence interval (CI) = 1.17–1.42, P = .001), female sex (OR = 2.69, 95% CI = 1.69–4.29, P < .001), African‐American race (OR = 1.55, 95% CI = 1.00–2.41, P = .05), and having inadequate financial resources (OR = 2.03, 95% CI = 1.22–3.38, P = .006). In the baseline unrestricted life‐space group, 49.5% (n = 49) had restricted life‐space at 90‐day follow‐up. Baseline restricted life‐space was associated with greater odds of 90‐day hospital readmission (unadjusted OR = 1.64, 95% CI = 1.00–2.70, P = .05; adjusted OR = 1.72, 95% CI = 1.04–2.85, P = .03).
Conclusion
Baseline restricted life‐space was associated with greater risk of hospital readmission within 90 days after hospital discharge. These findings suggest a need to customize the management of individuals hospitalized with CHF or COPD based on baseline life‐space level.
OBJECTIVES: To examine whether cytomegalovirus (CMV) and herpes simplex virus type‐1 (HSV‐1) are associated with cognitive decline over a 4‐year period and to assess whether C‐reactive protein (CRP) ...modifies these relationships.
DESIGN: Prospective cohort study over a 4‐year period.
SETTING: Community‐dwelling elderly population.
PARTICIPANTS: The sample was a subset (1,204/1,789) of participants in the Sacramento Area Latino Study on Aging (SALSA) aged 60 to 100.
MEASUREMENTS: Participants were screened annually over a 4‐year period for cognitive function and episodic memory. Cognitive function was assessed using the modified Mini‐Mental State Examination, and episodic memory was assessed using a word list‐learning test of delayed recall. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV‐1 and for levels of CRP.
RESULTS: There was a significantly higher rate of cognitive decline over the 4‐year period in subjects with the highest CMV antibody levels at baseline than in individuals with the lowest levels (β=−0.053, standard error =0.018; P=.003), after controlling for age, sex, education, income, and chronic health conditions. There was no association between HSV‐1 antibody levels and cognitive decline. CRP did not modify the relationship between viral antibody levels and cognitive decline.
CONCLUSION: This is the first study to show that individuals with higher levels of antibody to CMV experience a more‐rapid rate of cognitive decline than those with lower levels. Understanding the mechanisms by which CMV influences cognition may aid development of intervention strategies targeting infection, viral reactivation, and immune response over the life course.
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and ...cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998-1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 95% CI 1.10-6.60). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
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